Cervical Vulvovaginal and Penile Lesions PDF

https://webpath.med.utah.edu/EXAM/MULTORG/fem1frm.htm + Emboss Yesrself aftegyina I · s ↑...

https://webpath.med.utah.edu/EXAM/MULTORG/fem1frm.htm + Emboss Yesrself aftegyina I · s ↑ 2 - - 3 - - - Pathology department, BMC  = external superficial genitalia ① basal cells of squamous epi = - - œlls - O - - fiormalUterus = O Batterjee M e d i c a l College For Sc ogy  ignave Ojo & cer vix d scie Emalignant Premalignant and Malignant Neoplasms of the- = Cervix Premetignant I - - Worldwide, cervical carcinoma is the third most common cancer in 2 & women. malignant · - ? Decreasing....& Pap smear > - sample from cervix swap a- i jas is - ?.. 0 & -- ( E cervix. - (detecting cervical precursor lesions). si - Precursor lesions are usually defined as lesions earlier than in situ disease Situi In its original place. For example, in carcinoma in situ, abnormal cells are found only in the place where they first formed. They have not spread. Ttatrt r j t c Mch.tJ ion I tea I It t ' OF i’‹ z F F ry ri f/ '/ i’ F / T F›/F›r r  Jin--e -ea 54 50 58 , g5 Premalignant - - boths * - - Pathogenesis - of cervical carcinaud : & Cancer /1 (malignant) jis s 931 High-risk human ⑳ papilloma viruses (HPVs) are by far the most S DNA viruses. & important factor in the development of cervical cancer. 5 - - -/ - 90%) HPVs accordingability - ↳ High and low oncogenic = its * = risk. T to Xo &# Low oncogenic risk HPVs are the cause of the - between anns and vulva ana perianal - sexually transmihed vulvar, perineal, and lumps warts (condyloma acuminatum) - fish eye - & (especially HPV-6 & 11) /.. $6 & -0 - & 15 high risk HPVs (especially - S # HPV-16 & 18). flowerutterns C - & low ->causing warts & high > - cousing cancers  site attack (tmp) to always ① s t ask why? f HPVs infect E immature basal cells of the squamous epithelium in areas - of epithelial breaks, or immature squamous cells present at the -- squamocolumnar junction. - HPVs cannot infect the - mature superficial squamous cells that cover - the ectocervix, vagina, or vulva. & -9. + d basal cells what is the first site & % 13224 · by HPVs Pathogenesis (115 that infected ? basal cells - & or squamoculmonar junction superficial. * ocervix of Vagina e stratified - squamous ep; - · endocervix - > Columnar epi Ttatrt r j t c Mch.tJ ion I tea I It t ' OF i’‹ z F F ry ri f/ '/ i’ F / T F›/F›r r  ② Although HPV infects immature squamous cells, viral replication occurs in maturing squamous cells. & = or abnormal cells ? normal Og4 Normally, these more mature cells are arrested in the G1 phase of => - - > SGjs the cell cycle because tumor suppressor genes (as TP53 and RB =>> = genes) inhibit & - ↳ - transition. E2F transcription factors that promote G1 to S phase - - artigThe ability of HPV to act as a carcinogen depends on the viral proteins E6 and E7, which interfere with the activity of tumor suppressor genes - & = - & & that regulate cell growth and survival. - & G1 —Growth & what Prevent- tumor supressor genes activity ? S - DNA synthesis the Viral Proteins EG and EF. ↑ ① G2 - Growth and & which of the followings is the cause of Ho to preparation for cause cancers ? EG and EF mitosis - - 3) M - Mitosis (cell division)  - & Rb gene. - - Oncoprotein E6 inhibits TP53 gene. Oncoprotein E7 inhibits Inactivation of these tumor suppressor genes leads to the - ①continued growth and proliferation of damaged cells + ② impairs the ability of cells to repair DNA damage.... prone - to acquire additional mutations that may lead to cancer④ development. ③ ‫ يضعف قدرة اخلاليا على إصالح تلف‬+ ‫يؤدي تعطيل هذه اجلينات الكابتة للورم إلى استمرار منو وانتشار اخلاليا التالفة‬.‫ مما يجعلها عرضة الكتساب طفرات إضافية قد تؤدي إلى تطور السرطان‬.... ‫احلمض النووي‬ > - By contrast to high-risk HPVs, the & # - E7 proteins of low risk = - - > - HPVs bind RB with lower affinity, while the & E6 proteins of - - - low-risk HPVs fail to bind p53 altogether and instead - - => - appear to dysregulate growth and survival..... ?? D & 5 Tsts risks , refl is highrise & 15 E , et j s low HPVs RB HPVs TP53 + D "9 , G -51 * E7- -5 8 - - warts not cancers. 19  I & S - & E & Intraepithelial& Cervical& Neoplasia , 55. (Squamous Intraepithelial Lesions) e um 1959 CE N b VIN cerriy signi & vnivol servicall raginall hyperplasia / - / - dysplasia - carcinoma in sity => - Atypic t & milddi -in ectocervix both ↑ &. jid · Endo + - · have ep; & - - b Premalignant %1 % 39 S JCINS js ·. 5, & - 30 BM & 11 J s & · Ti - - BMS A malignant A term used to describe the presence of abnormal cells within a tissue or organ. Dysplasia is not cancer, but it may sometimes atypia represents a benign process in many instances, while become cancer dysplasia describes a pre-neoplastic/neoplastic process1 Baue@ee Med1ca1 COMege ertce oztcf Wecftrto/opy  Situ : In its original place. For example, in carcinoma in situ, abnormal cells are found only in the place where they first formed. They have not spread. Carcinoma in situ is when cell changes appear cancerous under a microscope but have not spread beyond where they first formed. The words in situ mean in its original place. These in situ cells are not malignant, or cancerous. Carcinoma in situ refers to a group of abnormal cells that have not spread from the location where they first formed, although they may later spread into normal tissue and become cancer ① Carcinoma & in situ : /9 5ujx % ·:in maignant · 55s 5168 Acetowhite areas (5% acetic acid solution) : Premalignant - & L ·E j - %= risk high Batterjee M e d i c a l College HOUS  MORPHOLOGY ① Premalignant- & ↳ t BM 1② the whole epi basal cells (Immature) ⑦ lower malignant > - Lower 113 > - 213 - - Severe dysplasia isattacks the CINII · - high SIN B3M - carcinoma in Situ Batterjee M e d i c a l College For Science and Technology  ① pantthe -s , 55a Nuclear atypia refers to abnormal appearance of cell nucle Premalig The diagnosis of & diagnosis of CIN's based on identification of nuclear atsoia SIL is based on identification of & nuclear atypia - & characterized by...... + atypia- a nuclear atpi a squamousIntraepithel The nuclear changes are often - accompanied - by cytoplasmic - sE “halos.” These “halos” consist of = - = g : -8 perinuclear vacuoles, a change - O & · created by an HPV-encoded protein called & E5 that localizes to - - the membranes of the endoplasmic reticulum. O Nuclear atypa + - perinuclear halo are termed& & koilocytic atypia. b & halos + Koilocytes are epithelial cells characterised by perinuclear atypic Koilocytosis + haloes surrounding condensed nuclei = Koliotic. * *“’N,'.’,.„,'*,.*.J,./ /,’,'/„:„eatypiae /„.“,'*"'*°*‘” - - usPerchromatism atypic nudei large Pleomorphism  % 11 e Enzo CIN1-555 hyperenlarg chromation Atypia - :rude & crease Y shasaa a Prognosis Progression to invasive carcinoma, when it occurs, takes place over a 20 period of a few years to more than a decade. years B a u e @ e e Med1ca1 COMege ertce oztcf Wecftrto/opy  · medignat remembercom ene a Cervical & Carcinoma The average age of patients with invasive cervical carcinoma is#45 years. & - Squamous cell carcinoma is the most common histologic subtype (800/oof - or 90 % cases).of cervical - carcinoma The second most common tumor type is adenocarcinoma (150/oof cases). - I O ⑪ erd Adenosquamous and neuroendocrine carcinomas (50 /oof cases). All of tumor types are caused by high-risk HPVs. - -518 The progression time from in situ to invasive adenosquamous and - Joneuroendocrine carcinomas is shorter than in squamous cell and i adenocarcinomas, and patients with these tumors often present with - advanced disease and have a less - - favorable prognosis. " · & MORPHOLOGY squamous D cen carcinoma outside ze canal & of cervix D Gross:- Invasive cervical carcinoma may manifest as either fungating - (exophytic) or infiltrative masses. - inside+ - can B a u e @ e e Med1ca1 COMege ertce oztcf Wecftrto/opy  Description: Tumour of Uterine Cervix.” Sagittal cut section o af uterus showing an irregular, ”” ” ’. poorly-defined cervical mass. There is gross invasion into the cervical stroma with haemorrhage and necrosis. The necrosis is evidenced by the presence of irregular areas of cavitation within the tumour mass. ' ’ Uterus Cervix Irregular & poorly-defined borders with gross invasion into stroma Cavitation due to tumeur necrosis Diagnosis: Carcinoma of the Uterine cervix Bar (Histology : Squamous cell carclnoma) For  -> cell nests + Pearls + desmosomes & a squamous - gijs Microscopic: - of cervical Cancer : a cell nests BM O 1. - Squamous cell carcinoma ① Composed nests - malignant squamous epithelium, either keratinizing ;;j *tij.*-,;’' - non-keratinizing, = which invade the underlying cervical stroma. - ⑤ - Keratin pearls + desmosomes. or cell nests + desmosomes. - P.” M.-Ji-. 0 1 all. ⑳0 - zen.  epithelial cell proliferation The multiplication or reproduction of epithelial cells, resulting in the expansion of a cell population 2. Adenocarcinoma Characterized by proliferation of -glandular epithelium composed of - 80 A type of tissue that lines certain internal Q malignant endocervical gland - organs and makes and releases substances in the body, such as mucous, digestive juices, and other fluids. Glandular epithelium is commonly found ② large, hyperchromatic nuclei and - - in the breast, lung, stomach, colon, pancreas, prostate, uterus, and cervix. Also called glandular tissue. relatively ijs mucin-depleted 1591j8 & - - 81e - 25 - - cytoplasm, resulting in a dark I - appearance of the glands, as - compared to the normal endocervical epithelium. bc mucin deplec of ·:.05S1 s adenocarcinomas) 3 A Cytoplasm also ? endocervicaldis gland Batterjee M ed ical C o l l e g e ja , , For S ogy = 1221 3. Adenosquamous carcinoma Composed intermixed malignant glandular and squamous epithelium. ba den - - P.” M.-Ji-. 0 1 all.  - & All details are required (refer to lung tumors) I -55558 Immunohistochemistry (IHC) uses antibodies to detect antigens in a tissue sample - -  Spread of cervical cancer - ① Advanced cervical carcinoma spreads by - direct extension to i contiguous tissues, including paracervical soft tissue, - urinary bladder, ureters (resulting in hydronephrosis), E - rectum, and vagina. - & ① ⑬ - Lymphatic invasion results in local and distant lymph - - - nodes metastases. - then ③ & Blood and distant metastases may also be found in the G- going liver, lungs, Bone marrow, Brain and other organs. -- - BBLL Metastasis is when cancer spreads beyond the place where it started to other areas of your body. Nearly all cancers have the potential to metastasize.  O-Premalignant & 3 Stage & O names : E(Dr.) & make ⑥ Premalignant Eng - sure D Carcinoma in Situ malignant & CEN3 Staging or carcinoma in sity & HSIL & severe dysplasia ⑤ bowen's - ⑦ ⑨ dysplasia severe & Stage 0—Carcinoma in situ (CIN III, HSIL) & Stage II—Carcinoma extends beyond No invasion basement membrane the cervix but not to the pelvic wall. Carcinoma involves the upper vagina &Stage I—Carcinoma confined to the but not the lower third. - -- 198 -I -lax cervix = 11 & Stage III—Carcinoma has extended to A & la— diagnosed by microscopy up to Do there is no cancer-free space between 5ml the pelvic wall. On rectal examination - & Ia1-Stromal invasion not deeper than 3 the tumor and the pelvic wall. The = mm and not wider than 7 mm (so-called tumor involves the lower third of the ① microinvasive carcinoma) - E vagina. easy 8 give Ia2—Maximum depth of invasion E 3-5 · Stage IV—Carcinoma has extended mm; horizontal invasion not more than 7 beyond the true pelvis or has involved mm the mucosa of the bladder or rectum. - - -. Ib—confined to the cervix and more This stage also includes cancers with B 8 than & e metastatic dissemination. - - 5mll deeper & Ttatrt r j t c Mch.tJ ion I tea I It t. / rJ/'.Tra’‹ z r r yriz/ '/ r'r / T r›/r›r/ry T î at T1a2 i:1c Mls.e rÎ i.1inc iSr«i uftl \ by e›1i‹ r‹w c›[3\ Batterjee M e d i c a l C o l l e g e For Science and Technologiy  Cervical Cancer Stage Stage 2 Stage 3 Stage 4 Cancer is found Cancerous cells have spread to Cancer has spread to the Cancer has spread beyond the only in the cervix. the upper part of the vaglna or lower part of the vagina or the pelvis to the bladder, rectum, the tissue around the uterus. pelvic sidewall. Cancerous abdomen, liver, or lungs. cells may have also spread to the ymph nodes n the pelvi Batterjee M ed ical C o l lege Ft r S o ru:I Te hn c'gy Clinical Features of cervical cancer after ① - seX Presented by abnormal vaginal bleeding (Post-coital, menorrhagia, & - metrorrhagia, after menopause), unusual vaginal discharge which - ② may contain some blood or pelvic pain. -. - - cervix - 14 > - While early invasive cancers of the cervix (microinvasive carcinomas) - may be treated by cervical cone excision alone, most invasive -1 5515 => cancers are managed by hysterectomy I with lymph node dissection - and, for advanced lesions, radiation and chemotherapy. - - - - - The prognosis and survival for invasive carcinomas depend on the stage of the cancer at diagnosis and to some degree on histologic subtype, with small-cell neuroendocrine tumors having a very poor prognosis. enterns & hyster Ttatrt r i t e Mch.cJ wa I tea I It t. ** * N F' T’T*PT F 'F° ZJ P4 Z/ */ F’ F '/t I I F7/F/Z 5  %50 ‫ لألورام السرطانية اجملهرية وأقل من‬%100 ‫مع العالجات احلالية فإن معدل البقاء على قيد احلياة ملدة خمس سنوات هو‬.‫لألورام التي متتد إلى ما هو أبعد من احلوض‬ ① Clinical Features i ess S, 2009 5 = 5.5 =xjt-(a) = 3419x Istziase, Derv Sis, So Gl , · & -of With current treatments the 5-year survival rate is 100% for 5 microinvasive carcinomas and less than 50% for tumors of before strage extending beyond pelvis.perower & a d Pelic de Dat Most patients with advanced cervical cancer die of the -- => consequences of local tumor invasion- - e. ureteral - obstruction, pyelonephritis, hydronephrosis and uremia) - - - rather than distant metastases. ,‫ التهاب احلويضة والكلية‬,‫ميوت معظم املرضى املصابي بسرطان عنق الرحم املتقدم بسبب عواقب غزو الورم املوضعي )مثل االنسداد‬.‫ وتضخم احلالب البولي( وليس بسبب النقائل البعيدة‬,‫استسقاء الكلية‬  Vulval and penile lesions white Gav Patch - agnostic - ↓ Leukoplakia is a clinical term for opaque, white, plaque-like epithelial severe itching - thickening that may produce pruritus and scaling. - - >on - Vulva or - - Penis - May be caused by a variety of disorders, including the following: ① ② ⑪ Inflammatory dermatoses (e.g., psoriasis, chronic dermatitis). -- ⑪ ⑫ - Non-neoplastic epithelial disorders: Lichen sclerosus and squamous - & - cell hyperplasia. - - - - ① of Neoplasias: vulvar/penile intraepithelial neoplasia (VIN/PeIN), and - -Premignant invasive carcinoma. a causes of Leukoplakia on Vulva or Penis : ③mesigne D inflammatory dermatosis ② Psoriasis chronic dermatitis ⑨ Lichen sclerosus squamous cel hypeplasia ① VIN PIN ⑧ invasive carcinoma  that NON-NEOPLASTIC EPITHELIAL DISORDERS Cause leukopladic Ekera Kera epidermis - - dermis => & - Lichen sclerosus: 08 There is marked Squamous cell hyperplasia: ① thinning of epidermis sclerosis - displaying thickened epidermis and of the superficial dermis, and - ② ⑤ hyperkeratosis. & ↓ chronic ③ inflammatory cells in - lichen > deeper - dermis. mpnoges - macrophages Ttatrt r i t e Mch.cJ wa I tea I It t * N F' T’T*PT F 'F° ZJ P4 Z/ */ F’ F '/t I I F7/F/Z 5  - SIL ? SQUAMOUS - CARCINOMA IN SITU (VULVAL/PENILE > - INTRAEPITHELIAL NEOPLASIA PeIN) VIN - PIN (Bowen disease) = & sever dysplasia 2 ① CING stage o premate quart * - Bowen disease is associated * CIN3 Carcinoma & in Situ with high-risk HPV, most HSIL & full thickness affected commonly HPV O 16. (CIN3 8) & * - edysplasia Dysplastic - squamous cells & & squamous VIN a PIN Carcinoma in Situ containing②large hyperchromatic => ④irregular = > nuclei and ⑯lacking orderly maturation. Mitoses are - - - numerous. In # 10% of patients, = Bowen order In come , disease gives rise to invasive - - & In sitz carcinoma (Squamous cell carc.) -- Ttatrt r j t c Mch.tJ ion I tea I It t ' OF i’‹ z F F ry ri f/ '/ i’ F / T F›/F›r r A 49-year-old woman comes to the physician for a routine health maintenance examination and Pap smear. Her last Pap smear was 3 years ago and showed no abnormalities. She has smoked 1 pack of cigarettes daily for 32 years. She takes no medications apart from a multivitamin supplement. Physical examination shows no breast masses. The external genitalia. vagina, and cervix appear normal. The uterus and adnexa are normal to palpation. A Pap smear shows moderate epithelial dysplasia - of half of the - developing which of the following? 3 CIN2 basal epithelium and several koilocytes at the squamocolumnar junction. Without treatment, this patient is at greatest risk of KEYtNFO ATTENDINGTIP LABS NOTES @ MARK {}j SAVE FEEDBACK A Paraneoplastic polycythemia X B Superior vena cava syndrome S Obrain D C' Leptomeningeal metastases - X D Postrenal azotemia Pericardial effusion X Batterjee M e d ical C o l l e g e F o r Science o rid Technology